1. Field
The present disclosure relates to the synthesis of novel daidzein analogs as a method of treating and preventing breast cancer.
2. Description of Related Art
Breast cancer remains the predominant form of carcinoma affecting American women today and resistance to chemo- and endocrine therapy is a major cause of treatment failure in breast cancer. Worldwide, more than 1 million women are diagnosed with breast cancer every year, accounting for one-tenth of all new cancers and 23% of all female cancer cases. In 2009 alone there were an estimated 192,370 new cases of breast cancer and 40,610 deaths from the disease. Recent estimates of the lifetime risk of developing breast cancer for women born in the United States is now 1 in 8, an increase from 1 in 10 during the 1970s. Short of prevention, detection of breast cancer at an early, still curable stage would offer the best route to decrease its mortality rates. However, only 63% of breast cancers are still confined to the breast at the time of diagnosis. In addition, despite the survival benefit achieved by regional treatment and adjuvant systemic therapy, 30-50% of breast cancer patients will eventually develop metastatic relapse and die, while a small percentage of patients would have survived without these treatment modalities. Hence, better markers for early diagnosis, accurate prognosis and prediction of response to treatment are warranted to improve breast cancer care.
Treatment options traditionally include surgical intervention, chemotherapy, radiation therapy, and adjuvant systematic therapies. Breast-conserving surgery (lumpectomy) followed by local radiation therapy has replaced mastectomy as the preferred surgical approach for treating women with early stage breast cancer. Adjuvants may include but are not limited to chemotherapy, radiation therapy, and endocrine therapies such as administration of LHRH agonists; antiestrogens, such as tamoxifen; high-dose progestogens; adrenalectomy; and/or aromatase inhibitors.
Endocrine therapy has emerged as a promising new way to combat certain cancers. By blocking hormones that encourage cell growth and proliferation, endocrine therapy has been shown to be effective in preventing the growth of several carcinomas, including those developing in the breast and prostate. The administration of endocrine therapy for breast cancer is dependent on the presence of estrogen receptors on cancer cells. Growth of cancers cells that are estrogen receptor positive is affected by the level of estrogen. By contrast, growth of estrogen receptor negative cells is largely independent of estrogen levels. An endocrine therapy, comprised of selective estrogen receptor modulators (SERMs), is given to patients diagnosed with estrogen receptor positive breast cancer. Tamoxifen is the pharmaceutical composition used as a SERM for breast cancer treatment, and acts as an estrogen antagonist on breast tissue.
Tamoxifen has been shown to drastically reduce incidences of treatment failure in patients diagnosed with estrogen receptor positive breast cancer. Tamoxifen is also given to women who have a high genetic disposition for breast cancer as a preventative measure. While effective against forms of breast cancer, Tamoxifen acts as an agonist on uterine tissue and promotes endometrial cell proliferation, increasing the risk of uterine cancer in women. Furthermore, Tamoxifen has also been shown to increase the risk of blood clots. The National Cancer Institute has stated the need for better SERMs for use in the treatment of breast cancer.
There is a need to develop new SERMs to treat estrogen receptor positive breast cancer. Thus, in view of the anti-estrogen effects and ability to inhibit cell proliferation, the efficacy of novel daidzein analogs as a novel therapy in vivo was determined.
While certain novel features of this disclosure shown and described below are pointed out in the annexed claims, the disclosure is not intended to be limited to the details specified, since a person of ordinary skill in the relevant art will understand that various omissions, modifications, substitutions and changes in the forms and details of the disclosure illustrated and in its operation may be made without departing in any way from the spirit of the present disclosure. No feature of the disclosure is critical or essential unless it is expressly stated as being “critical” or “essential.”